miR-15/16 Restrain Memory T Cell Differentiation, Cell Cycle, and Survival

John D. Gagnon; Robin Kageyama; Hesham M. Shehata; Marlys S. Fassett; Darryl J. Mar; Eric J. Wigton; Kristina Johansson; Adam J. Litterman; Pamela Odorizzi; Dimitre Simeonov; Brian J. Laidlaw; Marisella Panduro; Sana Patel; Lukas T. Jeker; Margaret E. Feeney; Michael T. McManus; Alexander Marson; Mehrdad Matloubian; Shomyseh Sanjabi; K. Mark Ansel

Cell Reports (Aug 2019)

miR-15/16 Restrain Memory T Cell Differentiation, Cell Cycle, and Survival

John D. Gagnon,
Robin Kageyama,
Hesham M. Shehata,
Marlys S. Fassett,
Darryl J. Mar,
Eric J. Wigton,
Kristina Johansson,
Adam J. Litterman,
Pamela Odorizzi,
Dimitre Simeonov,
Brian J. Laidlaw,
Marisella Panduro,
Sana Patel,
Lukas T. Jeker,
Margaret E. Feeney,
Michael T. McManus,
Alexander Marson,
Mehrdad Matloubian,
Shomyseh Sanjabi,
K. Mark Ansel

Affiliations

John D. Gagnon: Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA
Robin Kageyama: Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA
Hesham M. Shehata: Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA
Marlys S. Fassett: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA
Darryl J. Mar: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA
Eric J. Wigton: Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA
Kristina Johansson: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA
Adam J. Litterman: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA
Pamela Odorizzi: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Dimitre Simeonov: Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA
Brian J. Laidlaw: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA
Marisella Panduro: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA
Sana Patel: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA
Lukas T. Jeker: Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA
Margaret E. Feeney: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Michael T. McManus: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA
Alexander Marson: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Mehrdad Matloubian: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Shomyseh Sanjabi: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA
K. Mark Ansel: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA; Corresponding author

Journal volume & issue: Vol. 28, no. 8
pp. 2169 – 2181.e4

Abstract

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Summary: Coordinate control of T cell proliferation, survival, and differentiation are essential for host protection from pathogens and cancer. Long-lived memory cells, whose precursors are formed during the initial immunological insult, provide protection from future encounters, and their generation is the goal of many vaccination strategies. microRNAs (miRNAs) are key nodes in regulatory networks that shape effective T cell responses through the fine-tuning of thousands of genes. Here, using compound conditional mutant mice to eliminate miR-15/16 family miRNAs in T cells, we show that miR-15/16 restrict T cell cycle, survival, and memory T cell differentiation. High throughput sequencing of RNA isolated by cross-linking immunoprecipitation of AGO2 combined with gene expression analysis in miR-15/16-deficient T cells indicates that these effects are mediated through the direct inhibition of an extensive network of target genes within pathways critical to cell cycle, survival, and memory. : Coordinate control of T cell proliferation, survival, and differentiation are essential for effective cell-mediated adaptive immunity. Gagnon et al. define roles for the miR-15/16 family of microRNAs in restricting T cell cycle and long-lived memory T cell accumulation through the direct inhibition of a very large network of target mRNAs. Keywords: microRNA, miRNA, miR-16, miR-15a, miR-15b, IL-7 receptor, CD127, Argonaute HITS-CLIP, cell cycle, T cell memory

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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